Peripartum depression affects up to one in seven women and is associated with significant maternal and neonatal morbidity if untreated. A history of depression is the strongest risk factor for developing peripartum depression. The U.S. Preventive Services Task Force recommends screening pregnant and postpartum women for depression. Both two-step and one-step screening strategies are effective in identifying peripartum depression. Peripartum depression should be distinguished from the baby blues, which is characterized by short duration, mild symptoms, and minimal impact on functioning. Women with peripartum depression should be evaluated for bipolar disorder, postpartum psychosis, and suicidal risk. For first-time mothers, adolescent mothers, and mothers who have experienced a traumatic delivery, home health visits, telephone-based peer support, and psychotherapy may help prevent peripartum depression. Mild to moderate depression should be treated with psychotherapy or selective serotonin reuptake inhibitors, whereas moderate to severe depression should be treated with a combination of psychotherapy and medication. Citalopram, escitalopram, and sertraline appear to be the safest selective serotonin reuptake inhibitors during pregnancy, whereas fluvoxamine, paroxetine, and sertraline are preferred in breastfeeding women because they lead to the lowest serum medication levels in breastfed infants. Patients with psychosis, active suicidal thoughts, or thoughts of harming their newborns should receive same-day psychiatric consultation and referral for possible inpatient treatment.